Author of

• 18975

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  P3.01 - Advanced NSCLC (ID 621)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23933

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    P3.01-074 - Genomic Analysis of Tumor and Plasma in T790M Mutant Positive EGFR Lung Cancer Patients before and after Osimertinib Treatment (ID 9224)

    09:30 - 09:30  |  Author(s): M. Shih
    • Abstract

    Background:
    Osimertinib is a third-generation, central nervous system active epidermal growth factor receptor (EGFR) – tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-sensitising and EGFR T790M resistance mutations. Osimertinib is approved for EGFR mutation positive non small cell lung cancer (NSCLC) patients who develop EGFR T790M resistant mutation and resistant to prior EGFR TKI. Osimertinib resistance pattern and clinical outcome after osimertinib treatment are undergoing intensive investigation.
    
    Method:
    Seventy-one EGFR-TKI resistant patients received osimertinib in the AURA study in one medical center. We excluded patients treated as first-line or who do not have detectable T790M mutation. We collect available data of pre-osimertinib treatment plasma and tissue and post-osimertinib plasma, tissue samples and tested for EGFR, HER2, K-ras, B-raf, mutations, ALK fusion and cMET or HER2 gene amplification. Clinical and pathological characteristics before and after osimertinib treatment were collected.
    
    Result:
    Of the 53 T790M-positive patients, 6 did not progress. Three and 18 patients discontinued osimertinib due to side effect or progression, respectively; 26 received osimertinib beyond progression (1.1 to 20.5 months); 7 patients received osimertinib combination after progression. Fourteen patients are still alive. Median progression-free survival(PFS), overall survival(OS) and post-progression survival (PPS) were 11.1 months, 16.9 months and 5.0 months, respectively (only progression patients). In 47 progressive patients, post progression EGFR plasma tests were available in 40 patients. T790M was detected by BEAMing in 12 patients (4 patients combined with C797S) and not detected in 28 patients (70%). OS and PPS was longest for patients with no detectable EGFR activating mutation and T790M in the plasma before and/or after osimertinib treatment. Patients who lost detectable T790M but maintained activating EGFR mutation in the plasma had shortest osimertinib PFS. Post progression tissue sample or pleural effusion tumor cells were available in 22 patients. Two patients developed small cell transformation, one patient developed squamous cell carcinoma. Post progression tissue or effusion genomic tests were performed (N= tested patient number) and showed T790M+ in 9 patients(N=18), C797S in 2 (N=12), cMET amplification in 5 (N=10), B-Raf V600 mutation in 1 (N=13), K-ras mutation in 1 (N=13) and no ALK, ROS1 and RET fusions.
    
    Conclusion:
    Heterogeneous resistance mechanisms develop after osimertinib treatment, in tumors retain T790M or losing T790M. Patients who have no detectable activating EGFR mutations in the plasma had best survival outcomes. Loss of T790M but maintainance activating EGFR mutations in the plasma correlated with short osimertinib PFS.